Cavaliere Fabio, Dinkel Klaus, Reymann Klaus
Research Institute for Applied Neuroscience, FAN GmbH, Leipziger Str., 44, D-39120 Magdeburg, Germany.
Exp Neurol. 2006 Sep;201(1):66-74. doi: 10.1016/j.expneurol.2006.03.020. Epub 2006 Jun 5.
A number of studies have already established the role of the subventricular zone in sustaining adult neurogenesis in different brain regions and under different pathological conditions, but nothing is reported about the role of this germinal area in preserving cell viability. In this work, we developed an organotypic culture model of the forebrain structures that comprise the neocortex, striatum, subventricular zone, and corpus callosum. With this model, we investigated the role of the subventricular zone in modulating cell viability in the cortex after oxygen/glucose deprivation. Here we have demonstrated that soluble heat-labile factors released by the subventricular zone in the media can lead to protection specifically in the cortical area. No protection was observed when medium, conditioned with factors released during the insult was administered to the hippocampal slices. Moreover, the use of different modifications of the slice cultures showed that the removal of the subventricular zone increased the cellular damage induced by oxygen/glucose deprivation. Furthermore, by using pharmacological experiments to investigate the possible mechanisms that regulate this subventricular function, we found evidence of purinergic involvement. We postulate that extracellular ATP signaling in the subventricular zone exacerbates cortical damage induced by hypoxia/hypoglycemia. For the first time, we demonstrate in vitro that the germinal subventricular zone can release factors that can be protective after exposure to a metabolic stressor. These released factors are not yet characterized but we identified in the extracellular ATP a factor that may interfere with the protective role of the subventricular zone during metabolic cortical damage.
多项研究已经证实了脑室下区在不同脑区以及不同病理条件下维持成体神经发生中的作用，但关于这个生发区在维持细胞活力方面的作用尚无报道。在这项研究中，我们构建了一个包含新皮层、纹状体、脑室下区和胼胝体的前脑结构的器官型培养模型。利用这个模型，我们研究了脑室下区在氧/葡萄糖剥夺后对皮层细胞活力调节中的作用。在此我们证明，脑室下区在培养基中释放的可溶性热不稳定因子能够特异性地对皮层区域起到保护作用。当将在损伤过程中释放因子所条件化的培养基应用于海马切片时，未观察到保护作用。此外，对切片培养进行不同处理的结果表明，去除脑室下区会增加氧/葡萄糖剥夺诱导的细胞损伤。此外，通过药理学实验来研究调节这种脑室下区功能的可能机制，我们发现了嘌呤能参与的证据。我们推测脑室下区的细胞外ATP信号会加剧缺氧/低血糖诱导的皮层损伤。我们首次在体外证明，生发的脑室下区能够释放暴露于代谢应激源后具有保护作用的因子。这些释放的因子尚未得到表征，但我们在细胞外ATP中鉴定出一种可能在代谢性皮层损伤期间干扰脑室下区保护作用的因子。
